Journal of affective disorders最新文献

Objective: To describe and compare the reporting patterns and signal strengths of male sexual dysfunction associated with six commonly prescribed SSRIs in the FDA Adverse Event Reporting System.

Methods: Adverse event data for six representative SSRIs, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram, were retrieved from the FAERS database, spanning from the first quarter of 2004 to the first quarter of 2025. Disproportionality analysis was conducted using both the reporting odds ratio (ROR) and proportional reporting ratio (PRR) to identify potential signals of adverse drug events associated with these medications.

Results: We analyzed 6,631,746 adverse drug event reports associated with SSRIs and detected significant disproportionality signals indicative of male sexual dysfunction in patients with depression. Across all SSRIs, erectile dysfunction was the most commonly reported adverse event [fluoxetine (ROR: 4.97, 95%CI: 4.25-5.82), paroxetine (ROR: 3.99, 95%CI: 3.53-4.5), sertraline (ROR: 6.11, 95%CI: 5.53-6.75), fluvoxamine (ROR: 1.08, 95%CI: 0.35-3.36), citalopram (ROR: 7.7, 95%CI: 6.81-8.69), and escitalopram (ROR: 7.93, 95%CI: 6.99-8.99)], followed by sexual dysfunction [fluoxetine (ROR: 11.94, 95%CI: 10.01-14.23), paroxetine (ROR: 11.39, 95%CI: 10.05-12.91), sertraline (ROR: 13.34, 95%CI: 11.86-15.01), fluvoxamine (ROR: 9.64, 95%CI: 5.01-18.56), citalopram (ROR: 15.09, 95%CI: 12.98-17.54), and escitalopram (ROR: 16.42, 95%CI: 14.11-19.12)].

Conclusion: This FAERS analysis detected significant disproportionality signals for male sexual dysfunction across SSRIs. Signal variation reflects reporting differences, not comparative risk, due to database limitations. These findings highlight the need for clinical vigilance and further investigation.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness associated with altered function in cortico-striatal-thalamo-cortical (CSTC) circuits. In this pilot study, we examined differential RNA expression in the thalamus using postmortem human brain tissue samples from 11 subjects with OCD and 10 unaffected subjects. We individually dissected the mediodorsal magnocellular, mediodorsal parvocellular, and ventral anterior nuclei, which participate in orbitofrontal and anterior cingulate CSTC circuits most frequently associated with OCD, and the posterior ventrolateral nucleus, which participates in premotor and motor circuits that are increasingly implicated in OCD. Preselected GABAergic, glutamatergic and ion channel genes were analyzed via qPCR. Two genes required for GABA synthesis and release, GAD1 and SLC32A1, were found to be downregulated in OCD subjects across all nuclei, and potassium channel KCNN3 was upregulated. In parallel, we performed an exploratory total RNAseq differential expression analysis. We identified few (12-52) differentially expressed genes (DEGs) in each nucleus, and only one DEG in a pooled analysis of all nuclei. No DEGs were significant after correction for multiple comparisons. Investigation by model selection indicated that OCD diagnosis was not a useful factor in modelling gene expression in our dataset. OCD was also not associated with any modules of co-expressed genes identified using weighted gene correlation network analysis. Overall, we found minimal evidence of differential RNA expression in these thalamic nuclei in OCD. These findings contrast with our previous work including many of the same subjects where we found widespread differential mRNA expression in the orbitofrontal cortex and striatum in OCD.

Paroxetine exhibits significant inter-individual variability in concentrations due to nonlinear pharmacokinetics and metabolic differences, particularly at higher doses. The therapeutic reference range recommended by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP; 20-65 μg/L) was derived primarily from studies in patients receiving 20-40 mg daily, which may not adequately reflect drug exposure at higher clinical doses. This study integrated literature data analysis and population pharmacokinetic (PPK) simulations, revealing that the mean concentration reported in the literature was 173.13 μg/L at 60 mg/d, significantly exceeding the AGNP range, while PPK simulations indicated a mean concentration of 235.94 μg/L in females at 60 mg/d, nearly twice that in males. Considering that sex and dosage significantly influence paroxetine concentrations, sex-specific exploratory therapeutic reference ranges for 60 mg/d were proposed: 85-180 μg/L for males and 150-290 μg/L for females. Based on clinical data and reported toxicity cases, a laboratory alert concentration of 350 μg/L is suggested to ensure an adequate safety margin. Overall, this study refines the paroxetine therapeutic reference range by incorporating dose- and sex-specific guidance to support more precise therapeutic drug monitoring (TDM) and promote individualized treatment, particularly at a dosage of 60 mg.

Objective: Research on the link between antenatal depression and alterations in offspring DNA methylation is sparse and inconsistent. This study aimed to provide a robust and rigorous test of the association between maternal antenatal depression and offspring DNA methylation in neonatal and middle childhood (8-10 years) periods.

Methods: Moderate to severe maternal antenatal depression was identified via a combination of diagnosis codes from outpatient and inpatient encounters during pregnancy and self-reported symptom severity on birth certificates. Offspring DNA methylation was quantified from dried blood spot and venous blood samples in the neonatal and middle childhood periods, respectively.

Results: Of 733 mothers with available data in the neonatal period, 53 (7%) experienced moderate to severe antenatal depression. In middle childhood, 15 (9%) of the 161 mothers with available data experienced moderate to severe antenatal depression. In the neonatal period, no probes passed false discovery rate (FDR) correction. In middle childhood, antenatal depression was associated with hypomethylation at two probes after adjustment and FDR correction: cg06112204 (in MAD1L1; β = -1.68, SE = 0.29) and cg17830140 (in POLRMT, β = -1.94, SE = 0.36). Both probes had a similar direction and magnitude when controlling for postnatal depression (β = -1.71, SE = 0.34 and β = -1.78, SE = 0.42, respectively). cg06112204 was also hypomethylated in the neonatal sample (β = -0.49, SE = 0.21), but cg17830140 was not (β = 0.07, SE = 0.22).

Conclusions: Methylation of other probes in the MAD1L1 gene have previously been associated with depression phenotypes in adolescents and adults, lending credibility to the finding that antenatal depression is associated with hypomethylation of cg06112204 in offspring.

Emotional flexibility, thought to reflect the ability to adapt to internal and external environmental stimuli, is associated with psychological well-being. Emotional inertia and network density, defined as stability and interconnectedness, respectively, of emotions, are aspects of emotion dynamics that represent low emotional flexibility. Studies examining biological substrates of emotional persistence are largely limited to emotional inertia and non-depressed samples. Heart-rate variability (HRV) is a transdiagnostic biomarker for psychopathology thought to be associated with emotional flexibility. This study examined whether emotional inertia and network density were associated with HRV in adults with moderate-to-severe depression (N = 315). Participants completed three 8-day epochs of ecological momentary assessment (EMA) five times daily. Smartwatches measured HRV throughout the study. Emotional inertia and idiographic networks were calculated separately for EMA-rated negative and positive affect. Bayesian dynamic structural equation models with noninformative prior distributions examined the association between emotional inertia and HRV; hierarchical linear modeling examined associations between network density and HRV. Both daytime and bedrest HRV were inversely associated with temporal network density of negative emotions. HRV was not associated with inertia, positive network density, or average EMA-reported affect, though it was associated with age, antidepressant medication, and physical exercise. This was the first study to examine HRV in relation to these emotion dynamics in a depressed sample. The results suggest that experiencing a variety of negative emotions within a short period of time may be associated with underlying biological inflexibility. Future studies should examine the directionality and mechanisms behind this effect and explore potential clinical interventions.

Background: The Suicide Crisis Syndrome (SCS) is a suicidal mental state and a proposed DSM diagnostic condition shown to predict short-term suicidal behaviors among clinical and non-clinical populations in the United States and worldwide. The goal of this study was to develop and assess the psychometric properties of a short clinician-rated SCS diagnostic tool, the SCS Checklist (SCS-C), to provide a structured assessment of patients' SCS through clinical interview.

Method: The SCS-C, a clinician-rated measure composed of 15 binary (yes/no) items was developed and administered to 219 patients upon admission into an inpatient psychiatric unit. Factor structure, internal and interrater reliability, concurrent construct validity (i.e., convergent and divergent validity), and concurrent criterion validity (within one week prior to inpatient admission) were respectively assessed using Confirmatory Factor Analysis, Cronbach's Alpha and McDonald's Omega, Cohen's Kappa, and linear and logistic regressions.

Results: The SCS-C demonstrated excellent fit for a one factor solution, high internal consistency (Cronbach's α = 0.87; McDonalds' Ω = 0.89), moderate convergent validity, good divergent validity, as well as good concurrent criterion validity with regards to suicidal behaviors.

Discussion: This study's findings suggest that the SCS-C is a psychometrically valid and reliable diagnostic tool to assess the presence of the SCS through a swift clinical interview, regardless of patients' disclosure of suicidal ideation. Given the persistent difficulty in evaluating suicide risk through patient self-report, this concise diagnostic tool holds substantial clinical promise for improving suicide risk detection and prevention. Future studies will need to investigate the predictive validity of the instrument.

Background: With population ageing and insufficient mental health workforce, there are huge treatment gaps for late-life depression. Real-world evidence of scalable preventive services is scarce. This study examines the effectiveness of an integrated selective and indicated prevention programme for late-life depression in a large group of older adults in Hong Kong.

Methods: This was a pragmatic quasi-experimental trial of a new service ("JoyAge") for older people with risk factors for late-life depression or subsyndromal depressive symptoms. Participants were recruited and allocated, based on their district of residence, to receive JoyAge (N = 2975) or usual care (N = 441). The primary outcome was depressive symptoms (PHQ-9) at 12-month follow-up; secondary outcomes were anxiety symptoms (GAD-7) and loneliness (UCLA-3). Analyses were conducted in an intention-to-treat framework using mixed modelling, with subgroup analyses based on baseline depressive symptoms, and sensitivity analyses in a 1:1 (N = 422 each group) propensity score-matched sample.

Results: The JoyAge participants had a greater reduction in depressive symptoms over the 12-month period compared to those assigned to usual care (adjusted mean difference [AMD] = 1.65, 95% CI = 1.24-2.07, p < .001), similarly in anxiety symptoms (AMD = 1.47, 95% CI = 1.01-1.93, p < .001), and loneliness (AMD = 1.29, 95% CI = 0.98-1.60, p < .001). Results were similar in propensity-score matched analyses. Subgroup analysis showed that JoyAge was particularly effective among people with moderate to moderately severe symptoms and those with risk factors only.

Conclusions: Integrated late-life depression prevention can be effectively implemented at scale in rapidly ageing settings with a limited specialist mental health workforce. Economic analyses are needed to support further implementation.

Objective: This study aims to investigate the bidirectional relationship and cascading effects of socioeconomic status (SES) and depression symptoms in middle-aged and older adults, with physical activity acting as a mediator.

Methods: A total of 23,747 adults (age ≥ 45 years) from the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), the Mexican Health and Ageing Study (MHAS), and the Survey of Health, Ageing and Retirement in Europe (SHARE) participated in this six-year longitudinal study. Socioeconomic status was categorized using latent class analysis. Physical activity depends on participants' frequency over the past two years. The Center for Epidemiologic Studies Depression (CESD) Scale and the European Depression (EURO-D) Scale was used to assess depressive symptoms. Cross-lagged models examined bidirectional associations.

Results: After adjusting for potential covariates, there was strong continuity across the three time points for socioeconomic status, physical activity, and depressive symptoms. Socioeconomic status and physical activity positively predicted each other, while depressive symptoms were associated with lower levels of physical activity.

Limitations: The limitations of this study include the exclusion of the indirect selection hypothesis and the reliance on self-reported depressive symptoms.

Conclusion: Physical activity mediates the relationship between depressive symptoms and subsequent socioeconomic status, with depression-related risks potentially having a greater impact on the socioeconomic status of middle-aged and older single women in developed countries, highlighting the need to consider additional factors in reducing depression risk among older adults.

Background: ADHD has been associated with impaired central nervous dopaminergic pathways. Brain iron is an essential cofactor for the synthesis of dopamine and the substantia nigra (SN) is a significant pool of dopaminergic neurons playing a central role in the activity of the nigrostriatal pathway. The present study investigated SN iron content in children with ADHD, its relationship with ADHD symptom severity and cognitive performance.

Methods: Neuroimaging and phenotypical data were extracted from the Healthy Brain Network dataset. After initial screening, 54 medication-naïve children with ADHD and 44 neurotypical (NT) children (8-12 year) were included. ADHD symptom severity was extracted from the Child Behavior Checklist (CBCL) Parent report and working memory (WM) and inhibitory control scores from the National Institute of Health toolbox.

Results: A mixed between-within subjects ANOVA revealed no significant difference in SN iron content between medication-naïve children with ADHD and NT (partial eta squared = 0.001, p = .79). In the ADHD group, Spearman's correlation revealed a significant inverse relationship between left (r = -0.38; p < .01) and right (r = -0.33; p = .01) SN iron content and CBCL Attention Problems T score, while in the NT group left SN iron content significantly correlated with inhibitory control (r = 0.36; p = .02).

Conclusions: Although there was no difference in nigral iron content between both groups, higher SN iron content was associated with lower attention problems in children with ADHD and higher SN iron content was associated with better inhibitory control in NT children.